Total parenteral nutrition (TPN) is an accepted treatment for severe malnutrition with marked gastrointestinal disease; such treatment is often associated with appearance of a disabling bone disease, characterized by normal or elevated serum Ca and P, normal or reduced serum iPTH, substantial hypercalciuria, an reduced serum levels of 1,25(OH)2D with normal levels of other vitamin D metabolites. Its cause is unknown. The morbidity of this bone disease, which occurs in patients whose lives have been prolonged by this treatment, may be profound. The goals of this proposal are to evaluate: 1) the mechanism responsible for altered vitamin D metabolism and/or PTH secretion and 2) the causes of the profound hypercalciuria; it is hoped to establish the cause of the metabolic bone disease and establish means for prevention of treatment. Protocols are planned to identify the course of the development of the biochemical abnormalities of Ca, P, vitamin D metabolites and PTH as TPN is initiated, to evaluate specific components in the TPN solution which may be "pathogenic" and evaluate the effects of various therapeutic manuevers, including parenteral 1,25(OH)2D3. The response to treatment will be evaluated by serial bone biopsies, with quantitative histomorphometric techniques, and by photon absorptiometric measurement of bone mineral content. The methodology also involves admission of these patients to the Clinical Research Center, with serial measurements of serum levels of vitamin D metabolities 25(OH)D2, 26(OH)D3, 24,25(OH)2D2, 24,25(OH)2D3, and 1,25(OH)2D), serum iPTH (using a sensitive C-terminal assay) and standard biochemical measurements. In these patients, who have obligate daily IV infusions the effect of human PTH (hPTH, 1-34) given by infusion, and the kinetics of 1,25(OH)2D administered intravenously, will be evaluated. The metabolism of vitamin D3, 25(OH)D3, and 24,25(OH)2D3 will be evaluated by treating these patients with UV light, since the only circulating vitamin D sterols in these patients are vitamin D3 derivatives. The study of these patients, who are unique with normal serum levels of vitamin D metabolites except for 1,25(OH)2D, may give insight into the physiologic effects of 1,25(OH)2D3 on bone. The data obtained may provide insight into the pathogenesis, management and prevention of this troublesome syndrome in these patients and to delineate factors controlling the metabolism of vitamin D and parathyroid hormone in man.